Why is there late replication?

It has been known for about 40 years that the S phase of the cell cycle is regulated and that parts of the genome are replicated early, while others a re replicated late. Numerous studies in the past two decades have revealed that while expressed genes, such as those coding for housekeeping proteins, are usually replicated early, genes not expressed in a particular cell and heterochromatic regions of the genome, such as the centromeres or the inac tivated X chromosome of females, are usually replicated late. As details of the mechanisms leading to the formation of replication complexes were work ed out, in particular for the budding yeast, Saccharomyces cerevisiae, new insights into the control of the order of replication of genes were obtaine d that indicate that this process is highly regulated. It is coordinated wi th transcription, epigenetic changes in chromatin structure, regulation of precursor pools and surveillance mechanisms.